Why isn't imiquimod cream used prior to performing a biopsy used for suspected facial basal cell carcinomas?

Question

Given a neoplasm of uncertain behavior of skin on a patient's face that is suspected to be a basal cell carcinoma (BCC), the typical first step is to perform a shave biopsy to determine the type of basal cell carcinomas so that one can decide the treatment {1}.

The downside of a shave biopsy is that it leaves a small scar.

The main 4 types of BCCs are:

• superficial: often treatable with imiquimod cream {2,3,4},
• nodular: sometimes treatable with imiquimod cream {2,3},
• micronodular: requires surgery (preferably Mohs if on face for cosmetic reason),
• infiltrative: requires surgery (preferably Mohs if on face for cosmetic reason).

Why isn't imiquimod cream used prior to performing a biopsy used for a suspected facial basal cell carcinoma?

Rationale: if imiquimod cream is successful in treating the BCC, no need to perform a biopsy.

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References:

• {1} Medscape (mirror):

  A skin biopsy is often required to confirm the diagnosis and determine the histologic subtype of basal cell carcinoma (BCC). Most often, a shave biopsy is all that is required. [Mar 2, 2020]

• {2} Bath-Hextall, Fiona, Mara Ozolins, Sarah J. Armstrong, Graham B. Colver, William Perkins, Paul SJ Miller, and Hywel C. Williams. "Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial." The lancet oncology 15, no. 1 (2014): 96-105. https://doi.org/10.1016/S1470-2045(13)70530-8

  Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion.

  [Note: I believe the statement "Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma" is incorrect, as from what I recall Mohs surgery has been shown to yield superior results compared to excisional surgery.]

• {3} https://dermnetnz.org/topics/imiquimod/

  Imiquimod is mainly used to treat: [...] Basal cell carcinoma (BCC), especially superficial BCC and sometimes low-risk nodular BCC

• {4} Raasch, Beverly. "Management of superficial basal cell carcinoma: focus on imiquimod." Clinical, cosmetic and investigational dermatology: CCID 2 (2009): 65. https://dx.doi.org/10.2147%2Fccid.s3507 ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047930/

  To date one long-term study indicates a treatment success rate [of Imiquimod for superficial BCCs] of 78%–81% and that initial response is a predictor of long-term outcome. Recurrences tend to occur within the first year after treatment.

Answer 1

Reddit user zumbusch nicely summarized the answer:

The biggest risk [of using imiquimod cream instead of performing a shave biopsy] would be improper treatment of another type of BCC such as infiltrative, or a different malignant lesion that was mimicking a superficial BCC, which would result in a delayed diagnosis and potential progression of disease before adequate treatment.

This was confirmed to me by several dermatologists at top ranked hospitals in the United States.

I'd further add two related risks:

1. The imiquimod cream may make it look as if the BCC was treated, while deeper cancerous cells may still exist (e.g., if the BCC is infiltrative): the tumor would further grow until it is visible at the surface of the skin again.
2. Treating with imiquimod cream may make it more difficult to treat BCC via a Mohs surgery afterwards, as it may make the border of the cancerous cell cluster less clear.